Current Status of Senolytics and Senomorphics: Mechanistic Insights, Clinical Progress, and Future Directions

Background: Cellular senescence contributes to aging, chronic inflammation, and age-related diseases. Senolytics eliminate senescent cells, whereas senomorphics modulate their pathological activities, including the senescence-associated secretory phenotype (SASP). This review examines their mechanisms, preclinical and clinical evidence, safety, and translational challenges. Methods: Published mechanistic, preclinical, and clinical literature on senolytic and senomorphic therapies was reviewed, focusing on therapeutic targets, disease-specific findings, safety, and clinical translation. Results: Senolytics, including dasatinib plus quercetin, navitoclax, and fisetin, target senescent-cell survival pathways, whereas senomorphics, including rapamycin, metformin, and Janus kinase inhibitors, modulate inflammatory signaling and SASP-associated pathways. Preclinical studies suggest benefits across metabolic, cardiovascular, musculoskeletal, and neurodegenerative disease models. However, human evidence remains limited and heterogeneous. Early clinical studies demonstrate the feasibility of senescence targeting and changes in selected biomarkers, but consistent clinical benefit remains unestablished. Major challenges include senescent-cell heterogeneity, insufficiently validated biomarkers, treatment-related toxicity, and the physiological roles of senescence in tissue repair and tumor suppression. Conclusions: Senolytics and senomorphics are promising but investigational therapeutic strategies. Clinical translation requires validated biomarkers, disease-specific patient selection, improved therapeutic selectivity, adequately powered trials with clinically meaningful endpoints, and long-term safety assessment. Aligning therapeutic strategies with senescent-cell phenotypes, disease context, and treatment objectives may improve clinical relevance.